Abstract
Background: Limb-girdle muscular dystrophy 2E (LGMD 2E), recently renamed as autosomal recessive limb-girdle muscular dystrophy-4 (LGMDR4), is characterized by the lack of beta-sarcoglycan, normally expressed in skeletal muscles and cardiomyocytes. We hypothesized that progressive respiratory and left ventricular (LV) failure in LGMDR4 could be associated with the age and interrelated phenomena of the disease's natural history.Methods: We conducted a retrospective review of the records of 26 patients with LGMDR4. Our primary objective was to compare the rates of decline among creatine phosphokinase (CPK) values, pulmonary function test (PFT) measures, and echocardiographic estimates and to relate them to patients' age.Results: The rates of decline/year of CPK, PFTs, and LV function estimates are significatively bound to age, with the LV ejection fraction (EF) being the strongest independent variable describing disease progression. Moreover, the rate of decline of CPK, PFTs, and LV differed in patients grouped according to their genetic mutations, demonstrating a possible genotype–phenotype correlation. The parallel trend of decline in CPK, PFT, and EF values demonstrates the presence in LGMDR4 of a simultaneous and progressive deterioration in muscular, respiratory, and cardiac function.Conclusions: This study expands the current knowledge regarding the trend of CPK values and cardiac and respiratory impairment in patients with LGMDR4, to optimize the monitoring of these patients, to improve their quality of life, and to provide clinical indices capable of quantifying the effects of any new gene or drug therapy.
Highlights
Limb-girdle muscular dystrophy 2E (LGMD 2E), recently renamed as autosomal recessive limb-girdle muscular dystrophy-4 (LGMDR4), is characterized by the lack of beta-sarcoglycan, normally expressed in skeletal muscles and cardiomyocytes
Limb-girdle muscular dystrophy 2E (LGMD 2E), recently reclassified as limb-girdle muscular dystrophy recessive type 4 (LGMDR4) [1], is a rare type of recessive muscular dystrophy caused by the lack of beta-sarcoglycan
More than 60% of LGMDR4 patients suffer from dilated cardiomyopathy [8], a condition that is less frequently observed in LGMDR3 and LGMDR5 [9]
Summary
Limb-girdle muscular dystrophy 2E (LGMD 2E), recently renamed as autosomal recessive limb-girdle muscular dystrophy-4 (LGMDR4), is characterized by the lack of beta-sarcoglycan, normally expressed in skeletal muscles and cardiomyocytes. Sarcoglycans (SGs) count four transmembrane proteins: alpha (a-), beta (b-), gamma (c-), and delta-sarcoglycan (d-SG), organized in a tetramer that stabilizes the Clinical Determinants in Beta-Sarcoglycanopathy dystrophin-associated glycoprotein complex [2] These proteins are expressed in the sarcolemma of smooth and striated muscular fibers. LGMDR4 is often associated with respiratory failure [10], a leading cause of death in affected individuals that is nowadays successfully prevented using non-invasive ventilation (NIV) [11] Aside from this little information, the natural history of LGMDR4 is still poorly known because of its rareness (prevalence is estimated around 0.86 × 10−6 individuals) and of the great difficulties in collecting data from so few and scattered patients. The present study was designed with the aim to improve the management and long-term outcome of LGMDR4 patients
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